Acute tryptophan depletion reduces kynurenine levels: implications for treatment of impaired visuospatial memory performance in irritable bowel syndrome

Kennedy, Paul; Allen, Andrew P.; O'Neill, Ann; Quigley, Eamonn Martin; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard

doi:10.1007/s00213-014-3767-z

Cited by 33 publications

(18 citation statements)

References 80 publications

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“…It was suggested that alternative pathways may also lead to memory impairments (e.g., LTP/NMDA related mechanisms). For example, ATD leads to lower kynurenic acid levels and has been associated with cognitive performance (Kennedy et al 2015). However, there is no clear evidence that the changes in kynurenic acid levels affect the cholinergic neurotransmission (e.g., Stone and Darlington 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Related to the discussion above, it should also be noted that BIP has a selective affinity for the M1 and M4 receptors (Perez et al 2006), whereas ATD has a global effect on serotonin and kynurenine (Badawy and Dougherty 2016; Kennedy et al 2015). Even though in this study a selective and a global challenge were combined, both methods are assumed to act on different neurotransmitter systems in the brain.…”

Section: Discussionmentioning

confidence: 99%

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Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

2017

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BackgroundResearch on the neurobiological foundations of memory has shown that multiple neurotransmitters play an important role in memory processing. To study the interaction between neurotransmitters such as acetylcholine and serotonin, pharmacological models can be used. In this study, we tested the effects of the muscarinic M1 antagonist biperiden, acute tryptophan depletion (ATD), and the interaction between the two on episodic memory using the verbal learning task.MethodsThe study was conducted according to a double-blind, placebo-controlled, four-way crossover design. Seventeen participants received biperiden (2.0 mg), ATD (SolugelP), a combination of both, or a placebo in counterbalanced order with a wash out of at least 7 days. A verbal learning task was performed while recording electroencephalography. The task consisted of an immediate and delayed recall as well as a recognition part.ResultsResults revealed decreased scores on the delayed recall after biperiden and ATD separately but no significant interaction between the two. However, the event-related potential components P3b, N400, and P600 did show an interaction during encoding.ConclusionThese results indicate that both BIP and ATD impair episodic memory. However, an interaction between the serotonergic and cholinergic system on memory performance is not supported.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

2017

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“…Exaggerated motor responses to food and, especially to lipids, have also been demonstrated in the small intestine in IBS 167 . Furthermore, tryptophan, the 5-HT precursor, and related compounds present in some foods could modulate psychological comorbidities and gastrointestinal symptoms in IBS 168 . Food-related symptoms could also be mediated through interactions between our diet, the products of digestion and the gut microbiota.…”

Section: Managementmentioning

confidence: 99%

Irritable bowel syndrome

Enck¹,

Aziz

Barbara

et al. 2016

Nat Rev Dis Primers

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761

774

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high population prevalence. The disorder can be debilitating in some patients, whereas others may have mild or moderate symptoms. The most important single risk factors are female sex, younger age and preceding gastrointestinal infections. Clinical symptoms of IBS include abdominal pain or discomfort, stool irregularities and bloating, as well as other somatic, visceral and psychiatric comorbidities. Currently, the diagnosis of IBS is based on symptoms and the exclusion of other organic diseases, and therapy includes drug treatment of the predominant symptoms, nutrition and psychotherapy. Although the underlying pathogenesis is far from understood, aetiological factors include increased epithelial hyperpermeability, dysbiosis, inflammation, visceral hypersensitivity, epigenetics and genetics, and altered brain–gut interactions. IBS considerably affects quality of life and imposes a profound burden on patients, physicians and the health-care system. The past decade has seen remarkable progress in our understanding of functional bowel disorders such as IBS that will be summarized in this Primer.

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“…Kynurenic acid inhibits inflammation in the 2,4,6‐trinitrobenzenesulfonic acid (TNBS) model of colitis in rats by blocking enteric NMDA receptors . Gut derived kynurenic acid may also have effects on the central nervous system by affecting mood and cognition …”

Section: Host Genetics Obesity Microbiome and Gut Healthmentioning

confidence: 99%

Beneficial actions of microbiota‐derived tryptophan metabolites

Galligan

2018

Neurogastroenterology Motil

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Tryptophan is an important dietary amino acid and it is the precursor for 5-hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells in the gut mucosa. Tryptophan is also metabolized by enzymes in the gut mucosa and also by enzymes produced by the gut microbiome. Diet and the microbiome can contribute to metabolic disease in part by causing intestinal inflammation and increased permeability. In this issue of Neurogastroenterology and Motility, Jennis et al. test the hypothesis that indole tryptophan metabolites produced by gut bacteria might be responsible for the anti-inflammatory and beneficial metabolic effects of the gut microbiome and Roux-en-Y gastric bypass surgery for weight loss by obese patients. The authors identified indole-3-propionic acid as the beneficial metabolite. A review of the literature also revealed the beneficial effects of tryptophan metabolites on diabetes and metabolic disease and on inflammatory bowel disease. Taken together, these data highlight another health benefit of the intestinal microbiome, which produces beneficial products from dietary amino acids especially tryptophan.

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Acute tryptophan depletion reduces kynurenine levels: implications for treatment of impaired visuospatial memory performance in irritable bowel syndrome

Abstract: Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls. These data may have important implications for reducing cognitive impairment in irritable bowel syndrome.

Cited by 33 publications

References 80 publications

Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG

Irritable bowel syndrome

Beneficial actions of microbiota‐derived tryptophan metabolites

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